1、ChapterDrugs used for the treatment of osteoporosis Department of pharmacologyLiming zhou2015.9Contents Osteoporosis Antiresorptive drugs Bone-forming drugs Mineralization drugsOsteoporosis Osteoporosis is a disease characterized by low bone mass(bone thinning)that leads to fragile bones and an incr
2、eased risk of fractures of the hip,spine,and wrist.Normal OsteoporosisSevere osteoporosisCommon symptoms:Back painStooped postureFracturesPrimary osteoporosisSecondary osteoporosisIdiopathic osteoporosisPostmenopausal osteoporosisSenile osteoporosisOsteoporosisrisk factorsFactors you cannot changeGe
3、nder Age;Body size;Ethnicity;Family historyFactors you can change Sex hormones;Anorexia nervosa;(神经性厌食症)Calcium and vitamin D intake;Medication use;Lifestyle;Cigarette smoking;Alcohol intake Osteoporosisdiagnosis The Bone Mineral Density Test(BDT)Detect low bone density before a fracture occursConfi
4、rm an osteoporosisdiagnosis if you already have one or more fracturesPredict your chances of having fractures in the futureDetermine your rate of bone loss and monitor the effects of treatmentOsteoporosisdiagnosisBone Mass DensityThe National Osteoporosis Foundation Recommends a BDT if:You use medic
5、ations that cause osteoporosis You have type I diabetes,liver disease,kidney disease or a family historyYou experience early menopauseYou are postmenopause over 50 and have at least one risk factorYou are postmenopause over 65 and never had a testComprehensive treatment forosteoporosis deals with:Pr
6、oper nutrition Exercise Safety issues to prevent falls MedicationsOsteoporosismedicationsAntiresorptive drugs:Bisphosphonates,calcitonin,estrogen Bone-forming drugs:Parathyroid hormone,androgenMineralization drugs:Calcium and vitamin DBisphosphonates(双磷酸盐双磷酸盐）PharmacologicalSlow bone lossIncrease bo
7、ne densityReduce the risk fracturesAntiresorptive drugsBisphosphonateclinical applicationOsteoporosis in men and postmenopausal womenPreventing and treating osteoporosis due to glucocorticoid steroid medicationsTreating high bloodcalciumlevels due to cancerTreatingmultiple myelomaor solid tumor canc
8、ers that have spread to the boneBisphosphonateside effectsq Nausea,abdominal pain and indigestionqRash and itchy skinqA temporary increase in parathyroid hormoneand serum transaminase（血转氨酶）（血转氨酶）CalcitoninuCalcitonin analogues(which are manufactured versions of calcitonin)can be useful for treating
9、osteoporosis by slowing the breakdown of bone.uCalcitonin is a delicate molecule that would be destroyed by the digestive tract,it must be taken by nasal spray or by injectionuWith side effects of nausea,vomiting and allergicrash et al.Estrogen Therapyapplication Estrogen therapy(ET)reduce bone loss
10、,increasebone densityin both the spine and hip,and reduce the risk of hip and spine fractures in postmenopausal women.ET is approved for preventing postmenopausal osteoporosisand are most commonly administered in the form of a tablet or skin patch（经皮吸（经皮吸收）收）.Estrogen Therapyside effects uTaking est
11、rogen alone increases a womans risk of developing cancer of the uterine lining(endometrial cancer).uTo reduce this risk,women who still have a uterus(who have not had a hysterectomy（子宫切（子宫切除）除）)should usually take a progestin in combination with estrogenuSelective estrogen receptor modulators(SERMS)
12、are drugs that act like estrogen at some receptors uIt acts like estrogen for preventing bone loss and improving cholesterol.uCurrently,only raloxifene（雷洛昔芬）（雷洛昔芬）that is approved to prevent and treat osteoporosis.Selective Estrogen Receptor ModulatorsBone-forming drugsParathyroid hormone(PTH)mechan
13、ismWith both catabolic and anabolic actions Low dose:PTH stimulate bone turnover and is associated with bone formation（成骨作用）（成骨作用）High dose:PTH increase the rate of bone resorption followed by slower rate of bone formation（破骨作用）（破骨作用）Parathyroid hormone(PTH)application Osteoporosis Primary parathyro
14、id function decline (Intake vitamins D and calcium together)Generally applies only to first aidAndrogen and anabolic hormonemechaismAndrogen can promote the synthesis of protein and collagen,stimulate bone formation and retention of calcium,phosphorus,and potassium.Androgen and anabolic hormoneappli
15、cationmale osteoporosisSide effect is bigger,the dose of treatment and the pros and cons of relationship is still in the further researchMineralization drugsCalciumAdding bone mineral and promoting bone mineralizationvitamin D3 Increase the absorption of dietary calcium and phosphorus,maintain the b
16、alance of calcium and phosphorus and increase the activity of osteoblastsCalciumapplicationAcute or chronic hypocalcemia;Tetany disease（手（手足抽足抽搐）Rickets（佝偻病）;Osteomalacia（软骨病）,osteoporosis,parathyroid function impairmentMagnesium poisoning counterpoison（镁中毒解救）（镁中毒解救）(One key piece of advice is to ta
17、ke your calcium in several small doses throughout the day).vitamin D3applicationOsteoporosisChronic renal failureFor treatment and prevention of vitamin D deficiencyPsoriasis（银屑癣）qOsteoporosis is a disease of bone that commonly occurs in elderly people,and is characterized by the degeneration of bon
18、e superstructure,a decrease of bone strength,an increase of bone fragility and thus an increased risk of fracture.q Drugs available for the prevention and treatment of osteoporosis are catalogued into three types in terms of their actions on affecting calcification and boneover.Key ConceptsqAntireso
19、rptive agents,including bisphosphonates,calcitonin,estrogen and iprioavone which decrease the rate of bone loses through inhibiting the activity osteoclasts（破骨细胞）（破骨细胞）.Key ConceptsqThe second group agents including fluoride,parathyroid hormone and androgens that promote bone formation by stimulating the activity of osteoblasts（成骨细胞）（成骨细胞）.Please describe the classification and characteristic of osteoporosis drugs?Review questions
